1.Mechanism of Ferroptosis in Cerebral Ischemia-reperfusion and Interventional Mechanism of Huoxue Huayu Jiedu Prescription Based on "Blood Stasis and Toxin" Pathogenesis
Jiayue HAN ; Danyi PAN ; Jiaxuan XIAO ; Yuchen LIU ; Jiyong LIU ; Yidi ZENG ; Jinxia LI ; Caixing ZHENG ; Hua LI ; Wanghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):51-60
ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury, as well as the protective role of Huoxue Huayu Jiedu prescription (HXHYJDF) against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups: sham group, model group, deferoxamine (DFO) group (100 mg·kg-1), low-dose HXHYJDF group (4.52 g·kg-1), medium-dose HXHYJDF group (9.04 g·kg-1), and high-dose HXHYJDF group (18.07 g·kg-1), with ten rats in each group. Except for the sham group, the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1st, 3rd, 5th, and 7th days post-reperfusion using the modified neurological severity scores (m-NSS). Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin (HE) staining and transmission electron microscopy. The contents of malondialdehyde (MDA), glutathione (GSH), divalent iron ions (Fe2+), and reactive oxygen species (ROS) in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and Western blot (WB) were used to detect the expression of iron death marker proteins glutathione peroxidase 4 (GPX4), ferroportin-1 (FPN1), transferrin receptor protein 1 (TfR1), and ferritin mitochondrial (FtMt) in brain tissue. ResultsCompared with the sham group, the mNSS score of the model group was significantly increased (P<0.01). HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced, and the intercellular space was widened. The nucleus was fragmented, and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded, and the mitochondrial cristae decreased. The matrix was lost and vacuolated, and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS increased significantly (P<0.01). The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased (P<0.01), and the expression of FtMt and TfR1 proteins was significantly increased (P<0.01). Compared with those of the model group, the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3rd and 5th days, respectively (P<0.05, P<0.01). The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS decreased significantly (P<0.05, P<0.01). The content of GSH in the low-dose HXHYJDF group increased significantly (P<0.01), and the contents of MDA and ROS decreased significantly (P<0.01). The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly (P<0.01), and the expression of FtMt and TfR1 decreased significantly (P<0.01). The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly (P<0.05), and the expression of TfR1 decreased significantly (P<0.01). WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose, medium-dose, and low-dose HXHYJDF groups were significantly up-regulated (P<0.01), and the expression levels of FtMt and TfR1 proteins were significantly down-regulated (P<0.01). ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury, improve the pathological morphology of the infarcted brain tissue, and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury, with increased levels of MDA, Fe2+, ROS, and TfR1 and decreased levels of FtMt, FPN1, GPX4, and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins, promoting the discharge of free iron, reducing brain iron deposition, alleviating oxidative stress, and inhibiting ferroptosis.
2.New insights into translational research in Alzheimer's disease guided by artificial intelligence, computational and systems biology.
Shulan JIANG ; Zixi TIAN ; Yuchen YANG ; Xiang LI ; Feiyan ZHOU ; Jianhua CHENG ; Jihui LYU ; Tingting GAO ; Ping ZHANG ; Hongbin HAN ; Zhiqian TONG
Acta Pharmaceutica Sinica B 2025;15(10):5099-5126
Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.
3.Treatment of skeletal class Ⅱ high angle malocclusion patient by clear aligner therapy combined with orthognathic surgery:A case report and literature review
Qi ZHANG ; Xiaoyuan XU ; Yumiao WU ; Han ZHANG ; Zhiqiang HU ; Jiamin YUAN ; Yuchen CUI ; Xianchun ZHU
Journal of Jilin University(Medicine Edition) 2025;51(2):508-515
Skeletal class Ⅱ malocclusion is characterized by maxillary protrusion,mandibular retrognathia,or a combination of both,and often accompanied by vertical dimensional discrepancies;treatment is complex,and combined orthodontic-orthognathic surgery is needed for the adult patients.Clear aligner therapy has gradually been applied in complex orthodontic cases.However,limited cases have been reported domestically and internationally regarding the application of clear aligner therapy combined with orthognathic surgery.This article presented a case of a patient with skeletal class Ⅱ high-angle malocclusion treated with the combined therapy and analyzed the clinical efficacy of the treatment appraoch to provide reference for the clinical practice.Extraction of impacted wisdom teeth 18,28,38,and 48,as well as orthodontic teeth 15,25,34,and 44,was performed in stages before orthodontic treatment.Clear aligner therapy was used for preoperative orthodontics.In sagittal plane,a super-complete class Ⅱ canine and molar relationship and a 13-14 mm overjet of the anterior teeth were established.The maxillary and mandibular arch morphology was matched horizontally.The orthognathic surgery included maxillary LeFort Ⅰ osteotomy,bilateral sagittal split ramus osteotomy(BSSRO)and chinplasty.Fine occlusal adjustment was conducted after operation.After treatment,the skeletal relationship between upper and lower jaw was corrected to normal;subspinale-nasion-supramental angle(ANB)was improved from 12.3° to 4.7°;the patient established the class Ⅰ canine and molar relationship,with normal overjet and overbite;root parallelism was good and there was no obvious root resorption;the facial soft tissue profile was significantly improved,and nasion-subnasale-pogonion angle(N-Sn-Pg)was improved from 143.9° to 162.8°.The curative effect was stable 1 year after operation.Clear aligner therapy can efficiently complete combined orthodontic and orthodontic surgery in the complex cases.Compared with the fixed appliance,it is more beneficial to the patients'need for beauty and the maintenance of periodontal health.
4.Ameliorative effect of total flavonoids from corn silk on urate nephropathy in rats and its mechanism
Jing LU ; Mengmeng LIU ; Yuewei HAN ; Xiaowei HUANG ; Yuchen WANG ; He LIN ; Tianzhu ZHANG ; Zhe LIN ; Guangfu LYU
Journal of Jilin University(Medicine Edition) 2025;51(4):929-938
Objective:To discuss the ameliorative effect of total flavonoids from corn silk(TFCS)on kidney injury in the rats with urate nephropathy,and to clarify the possible mechanism.Methods:Sixty male Wistar rats were randomly divided into control group,model group,positive control group[benzbromarone(BZM)group,5 mg·kg-1·d-1],low dose of TFCS group(20 mg·kg-1·d-1),medium dose of TFCS group(40 mg·kg-1·d-1),and high dose of TFCS group(80 mg·kg-1·d-1),and there were 10 rats in each group.Except for control group,the rats in the other groups were administered potassium oxonate(350 mg·kg-1)and adenine(70 mg·kg-1)by gavage for 4 weeks to establish the hyperuricemic nephropthy models.The rats in different doses of TFCS groups were treated with TFCS for 2 weeks.Speckle blood flow imager was used to detect the renal blood perfusion of the rats in various groups and the kidney coefficients of the rats in various groups were caculated;HE staining and Masson staining were used to observe the pathomorphology and fibrosis degrees of kidney tissue of the rats in various groups and enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of uric acid(UA),creatinine(Cr),blood urea nitrogen(BUN),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the serum and levels of β2-microglobulin(β2-MG)and microalbumin(ALB)in the urine of the rats in various groups;Western blotting method was used to detect the expression levels of urate transporter 1(URAT1),glucose transporter 9(GLUT9),and ATP-binding cassette transporter G2(ABCG2)proteins in kidney tissue of the rats in various groups.Results:Compared with control group,the renal blood perfusion volume of the rats in model group was significantly decreased(P<0.01).Compared with model group,the renal blood perfusion volumes of the rats in BZM group and low,medium,and high doses of TFCS groups were significantly increased(P<0.05 or P<0.01).Compared with control group,the kidney weight of the rats in model group was increased,with visible white granular spots on the surface,absence of blood color,and kidney volume was increased.Compared with model group,the kidney volumes of the rats in BZM group and medium and high doses of TFCS groups were decreased,with color tending toward that in control group,and the white granular spots on the surface were significantly reduced.Compared with model group,the kidney coefficients of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).The HE staining results showed there were no abnormalities in kidney tissue structure in control group,while there were a small amount of brown-yellow urate crystal deposition and interstitial connective tissue hyperplasia in model group;compared with model group,the kidney tissue damage and inflammatory infiltration were alleviated to varying degrees in BZM group and different doses of TFCS groups.The Masson staining results revealed no obvious collagen fiber deposition in control group,whereas significant blue collagen fiber deposition in kidney tissue of the rats was found in model group,and the collagen volume fraction(CVF)was increased compared with control group(P<0.01);compared with model group,the CVFs of the rats in BZM group and different doses of TFCS groups were decreased(P<0.01).The ELISA results showed that compared with control group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in model group were increased(P<0.01);compared with model group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).Compared with control group,the levels of β2-MG and ALB in urinary in model group were increased(P<0.01);compared with model group,the levels of β2-MG and ALB in urinary of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in BZM group and model group were increased(P<0.01),while the expression level of ABCG2 protein was decreased(P<0.01).Compared with model group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01),and the expression level of ABCG2 protein was increased(P<0.01).Conclusion:TFCS can significantly alleviate the kidney injury in the rats with urate nephropathy model,and its mechanism may be related to the downregulation of expression of URAT1 and GLUT9 proteins and upregulation of ABCG2 protein expression in kidney tissue.
5.Research progress on the application of knee braces in knee osteoarthritis
Han WANG ; Cheng GUO ; Yuxuan LIU ; Tian MA ; Yuchen LIU ; Fei LIU
International Journal of Surgery 2025;52(7):498-504
Knee osteoarthritis exhibits a high prevalence and significantly impacts patients′ quality of life. Although surgical interventions demonstrate definitive efficacy, their acceptance rate remains generally low among patients. While knee braces have been widely adopted internationally, domestic research in this field is still limited. International studies suggest that knee braces can be recommended as an early-stage intervention strategy for knee osteoarthritis. Knee braces encompass diverse designs, each with distinct advantages and limitations. Many researchers are actively refining existing brace technologies, while others are innovating novel biomechanical approaches to develop next-generation knee brace systems. Currently, no standardized treatment protocol exists for the use of knee braces in early-stage knee osteoarthritis. This study summarizes and analyzes the research on the application of knee braces in knee osteoarthritis.
6.Mid-Term Efficacy Evaluation of Laparoscopic Sacrocolpopexy vs Laparoscopic Pectopexy for Pelvic Organ Prolapse
Yuqin LEI ; Yuchen SUN ; Tianyi SUN ; Xuesong HAN ; Zhiwei ZHAO ; Yali MIAO
Journal of Sichuan University (Medical Sciences) 2025;56(4):1104-1111
Objective To evaluate the perioperative safety and mid-term outcomes of laparoscopic sacrocolpopexy(LSC)and laparoscopic pectopexy(LP)for pelvic organ prolapse(POP).Methods A retrospective analysis was conducted on 274 POP patients,including 178 who underwent LSC and 96 who underwent LP,between August 2017 and January 2023.The extent of prolapse and anatomical restoration were assessed preoperatively and postoperatively using the Pelvic Organ Prolapse Quantification(POP-Q)system.Quality of life outcomes were evaluated with validated questionnaires,including Pelvic Floor Distress Inventory-short form 20(PFDI-20),Pelvic Floor Impact Questionnaire-short form 7(PFIQ-7),and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12(PISQ-12).Postoperative patient satisfaction was assessed during follow-ups.Postoperative anatomical restoration,perioperative status,and postoperative complications,recurrence,and quality of life were compared between the two groups.Multivariate logistic regression was performed to identify postoperative risk factors for recurrence.Results The operative time in the LSC group was significantly shorter than that in the LP group(P<0.05).Intraoperative blood loss was higher in the LSC group compared to that in the LP group(P<0.05).The LSC group also exhibited higher rates of de novo stress urinary incontinence and constipation(P<0.05).The mean follow-up duration was(35.91±16.90)months.The positions of the indicator points(Aa,Ba,C,Ap,and Bp)in the POP-Q classification after the operation were all better than those before the operation.The PFDI-20 score,PFIQ-7 score,and PISQ-12 score all improved compared to those before the operation(P<0.05).Comparison of preoperative and postoperative PFDI-20,PFIQ-7,and PISQ-12 scores showed no intergroup differences.Compared with the LP group,the LSC group had the lower preoperative POP-Q measurements at points Aa and Ba(P<0.05),but superior postoperative measurements for all the indicator points(Aa,Ba,C,Ap,and Bp)(P<0.05).Recurrence occurred in 28 cases in the LP group and 4 cases in the LSC group,with the LP group presenting a significantly higher anatomical recurrence rate than the LSC group did(31.46%[28/89]vs.2.41%[4/166],P<0.05).The subjective cure rate(100%)and objective cure rate(97.59%)in the LSC group were superior to those in the LP group(88.76%and 68.54%,respectively;P<0.05).The results of the multivariate logistic regression analysis showed that,after adjusting for the confounding factors,including age,gravidity,parity,body mass index,and duration of POP,the risk of recurrence after LSC surgery was 0.044 times that after LP(odds ratio[OR],0.044;95%CI,0.015-0.133;P<0.001).Conclusion Mid-term outcomes of LP with partial cervical preservation appear inferior to those of LSC,with LSC demonstrating superior anatomical restoration and lower rates of anatomical recurrence.However,improvements in sexual function and quality of life are comparable between the two procedures.Further evaluation with larger sample sizes and longer follow-up is warranted to better characterize long-term outcomes.
7.Study on the clinical characteristics of Chinese and Western medicine in 474 children with genetically-related tic disorder
Yuchen HU ; Simeng WANG ; Zilin CHEN ; Fei HAN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):961-970
Objective This study aimed to analyze the impact of genetic factors on the clinical presentation of tic disorder and investigate the pathogenesis of tic disorder considering different sources of genetic influence and generations,along with the distribution characteristics of evidence from Chinese medicine.Methods Inclusion of 474 cases of tic disorder was assembled(from October,2020 to October,2023),and clinical data on the children,including gender,age of onset,disease duration,initial symptoms,severity,comorbidities,and family history,and TCM patterns were collected.Firstly,the children were divided into genetic and nongenetic groups based on family history,and their clinical manifestations were observed.Secondly,the age of peak incidence of tic disorder in China(6 or 9 years)was used as the age segmentation point to explore the influence of heredity on clinical manifestations at different ages and the distribution of TCM patterns.Finally,children with genetically-related tic disorder were selected as probands to carry out family studies.The morbidity of the first-degree,second-degree and third-degree relatives of the probands were investigated to analyze the morbidity characteristics and distribution of TCM patterns of children with tic disorder under different genetic types.Results Out of 474 children,226 cases(47.7%)belonged to the genetic group,and 248 cases(52.3%)to the nongenetic group.Compared with the non-genetic group,the genetic group had a younger age of onset(P=0.013),a longer duration of illness(P=0.011),a higher degree of severity(P<0.01),and more comorbid conditions(P=0.016).Children in the genetic group with an age of onset under 6 years accounted for a larger proportion of the liver-hyperactive and wind-driven pattern(26.5%)and a smaller proportion of the qi depression transforming into fire pattern(17.1%),which were significantly different from those in the non-genetic group(P=0.016).In the genetic group,146 cases(64.6%)were inherited from the father,80 cases(35.4%)from the mother,and there was no significant difference in the developmental characteristics of children with tic disorder from different sources of genetic influence.Furthermore,183 cases(81.0%)were inherited from the parent-child generation,26 cases(11.5%)from the second generation,and 17 cases(7.5%)from the third generation;the difference in initial symptoms between different genetic generations was statistically significant(P=0.042).Conclusion Children with genetically related tic disorder have a younger age of onset,their condition is more severe,and they are more likely to be comorbid with other psychiatric disorders.The variation in the distribution of Chinese medicine patterns among children with tic disorder of different ages of onset.
8.Effect of MEIS1 expression on survival in patients after radical gastrectomy and its value in prognostic evaluation
Jiaxin YI ; Yangyu ZHANG ; Yingli FU ; Yuchen PAN ; Yongjie HAN ; Jing JIANG ; Yanhua WU
Journal of Jilin University(Medicine Edition) 2024;50(5):1358-1364
Objective:To discuss the postoperative survival of the gastric cancer patients with different expression levels of myeloid ecotropic viral integration site 1(MEIS1),and to analyze the predictive value of MEIS1 expression in the prognosis evaluation of gastric cancer.Methods:In a gastric cancer survival cohort,215 patients who underwent radical gastrectomy were selected.Immunohistochemical staining was used to detect the expression levels of MEIS1 in both gastric cancer and adjacent normal tissues.The relationship between expression level of MEIS1 and the clinicopathological characteristics of the patients were analyzed by x2 test or Fisher's exact probability method;survival curves were plotted by Kaplan-Meier method;the differences in survival of the patients between MEIS1 high expression group and MEIS1 low expression group were compared by Log-rank test;multivariate Cox proportional hazards regression model was used to calculate the hazard ratios(HR)and 95%confidence intervals(CI)to assess the relationship between MEIS1 expression level and the survival of the gastric cancer patients.Results:The immunohistochemical staining result showed that the expression level of MEIS1 in gastric cancer tissue was decreased.The univariate analysis results showed that the patients with high MEIS1 expression had a longer overall survival than those with low expression(P=0.049),and had a better prognosis.The multivariate Cox proprotional hazards regression analysis results showed that the low MEIS1 expression and high TNM stage were the independent risk factors for poor prognosis of the patients with gastric cancer(HR=1.577,95%CI:1.011-2.460,P=0.045;HR=2.709,95%CI:1.708-4.297,P<0.001).Conclusion:The gastric cancer patients with low expression of ME1S1 have a shorter postoperative overall survival;MEIS1 is a promising biomarker for prognosis assessment of the patients after radical gastrectomy.
9.Research progress in orthodontics combined with other disciplines in treatment of tooth ankylosis
Yuchen CUI ; Peining ZHU ; Jiamin YUAN ; Fujia KANG ; Han ZHANG ; Xianchun ZHU ; Xianpeng ZHONG
Journal of Jilin University(Medicine Edition) 2024;50(6):1780-1786
Tooth ankylosis is a clinical condition where the tooth cementum directly fuses with the surrounding alveolar bone,leading to functional and aesthetic defects.The etiology involves genetic,metabolic,and local stimulation factors.The diagnosis of tooth ankylosis requires a combination of clinical manifestations and imaging examinations to improve the diagnostic accuracy.The treatment of tooth ankylosis presents significant challenges.Orthodontic treatment combined with other disciplines offers a new,comprehensive treatment approach,integrating traditional orthodontic techniques with osteotomy,distraction osteogenesis,orthodontic bone traction,corticotomy,dislocation,and autologous tooth transplantation techniques.The treatment of tooth ankylosis requires the cooperation of multiple disciplines,and the experts from orthodontics,oral surgery,and oral medicine collaborate to develop the optimal treatment plan.This comprehensive treatment method achieves better outcomes compared with traditional treatments.This review discusses the etiology,diagnosis,and orthodontic combined multidisciplinary treatment methods of tooth ankylosis,analyzes the advantages and disadvantages of various treatment options,evaluates the efficacy and risks,and provides new perspectives for the treatment of tooth ankylosis.
10.Progress in the application of absolute ethanol in interventional embolization treatment of peripheral arteriovenous malformations
Qianyun HAN ; Yuchen SHEN ; Deming WANG ; Lixin SU ; Xiao LI ; Xindong FAN
Journal of Interventional Radiology 2024;33(11):1244-1252
Arteriovenous malformations(AVMs)are a kind of high-flow vascular malformation.AVMs can be classified in many ways,including histo-embryological classification,hemodynamic classification,etc.At present,the two mainstream classification systems used to guide the embolization treatment of peripheral AVMs are proposed by Cho and Yakes respectively based on the angiographic morphology of the lesions.Interventional embolization is the first-line treatment for AVMs.Among the many embolization agents,absolute ethanol is a permanent liquid embolization agent.Absolute ethanol can directly destroy the vascular endothelial cells to achieve a good curative efficacy,therefore,it has been wildly used in the treatment of peripheral AVMs.Yakes classification combines the angiographic classification with absolute ethanol embolization therapy.During absolute ethanol treatment,close attention should be paid to the occurrence of complications such as elevated pulmonary artery pressure.Although there are challenges remaining in the treatment of AVMs,the rapid development of molecular genetics has made targeted drug adjunctive treatment for AVMs possible.Perhaps,the novel therapeutic mode of combination use of traditional therapy targeted drug may be able to make a breakthrough in the treatment of AVMs.

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